Congenital Adrenal Hyperplasia-Current Insights in Pathophysiology, Diagnostics, and Management

Hedi L Claahsen-van der Grinten; Phyllis W Speiser; S Faisal Ahmed; Wiebke Arlt; Richard J Auchus; Henrik Falhammar; Christa E Flück; Leonardo Guasti; Angela Huebner; Barbara B M Kortmann; Nils Krone; Deborah P Merke; Walter L Miller; Anna Nordenström; Nicole Reisch; David E Sandberg; Nike M M L Stikkelbroeck; Philippe Touraine; Agustini Utari; Stefan A Wudy; Perrin C White

doi:10.1210/endrev/bnab016

Congenital Adrenal Hyperplasia-Current Insights in Pathophysiology, Diagnostics, and Management

Endocr Rev. 2022 Jan 12;43(1):91-159. doi: 10.1210/endrev/bnab016.

Authors

Hedi L Claahsen-van der Grinten¹, Phyllis W Speiser², S Faisal Ahmed³, Wiebke Arlt^{4

5}, Richard J Auchus⁶, Henrik Falhammar^{7

8}, Christa E Flück⁹, Leonardo Guasti¹⁰, Angela Huebner¹¹, Barbara B M Kortmann¹², Nils Krone^{13

14}, Deborah P Merke¹⁵, Walter L Miller¹⁶, Anna Nordenström^{17

18}, Nicole Reisch¹⁹, David E Sandberg²⁰, Nike M M L Stikkelbroeck²¹, Philippe Touraine²², Agustini Utari²³, Stefan A Wudy²⁴, Perrin C White²⁵

Affiliations

¹ Department of Pediatric Endocrinology, Radboud University Medical Centre, Amalia Childrens Hospital, Nijmegen, The Netherlands.
² Cohen Children's Medical Center of NY, Feinstein Institute, Northwell Health, Zucker School of Medicine, New Hyde Park, NY 11040, USA.
³ Developmental Endocrinology Research Group, School of Medicine Dentistry & Nursing, University of Glasgow, Glasgow, UK.
⁴ Institute of Metabolism and Systems Research (IMSR), College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
⁵ Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
⁶ Division of Metabolism, Endocrinology, and Diabetes, Departments of Internal Medicine and Pharmacology, University of Michigan, Ann Arbor, MI 48109, USA.
⁷ Department of Molecular Medicine and Surgery, Karolinska Intitutet, Stockholm, Sweden.
⁸ Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
⁹ Pediatric Endocrinology, Diabetology and Metabolism, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.
¹⁰ Centre for Endocrinology, William Harvey Research Institute, Bart's and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
¹¹ Division of Paediatric Endocrinology and Diabetology, Department of Paediatrics, Universitätsklinikum Dresden, Technische Universität Dresden, Dresden, Germany.
¹² Radboud University Medical Centre, Amalia Childrens Hospital, Department of Pediatric Urology, Nijmegen, The Netherlands.
¹³ Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
¹⁴ Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
¹⁵ National Institutes of Health Clinical Center and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
¹⁶ Department of Pediatrics, Center for Reproductive Sciences, and Institute for Human Genetics, University of California, San Francisco, CA 94143, USA.
¹⁷ Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
¹⁸ Pediatric Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
¹⁹ Medizinische Klinik IV, Klinikum der Universität München, Munich, Germany.
²⁰ Department of Pediatrics, Susan B. Meister Child Health Evaluation and Research Center, University of Michigan, Ann Arbor, MI 48109, USA.
²¹ Radboud University Medical Centre, Department of Endocrinology, Nijmegen, Netherlands.
²² Department of Endocrinology and Reproductive Medicine, Center for Rare Endocrine Diseases of Growth and Development, Center for Rare Gynecological Diseases, Hôpital Pitié Salpêtrière, Sorbonne University Medicine, Paris, France.
²³ Division of Pediatric Endocrinology, Department of Pediatrics, Faculty of Medicine, Diponegoro University, Semarang, Indonesia.
²⁴ Steroid Research & Mass Spectrometry Unit, Laboratory of Translational Hormone Analytics, Division of Paediatric Endocrinology & Diabetology, Justus Liebig University, Giessen, Germany.
²⁵ Division of Pediatric Endocrinology, UT Southwestern Medical Center, Dallas TX 75390, USA.

Abstract

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders affecting cortisol biosynthesis. Reduced activity of an enzyme required for cortisol production leads to chronic overstimulation of the adrenal cortex and accumulation of precursors proximal to the blocked enzymatic step. The most common form of CAH is caused by steroid 21-hydroxylase deficiency due to mutations in CYP21A2. Since the last publication summarizing CAH in Endocrine Reviews in 2000, there have been numerous new developments. These include more detailed understanding of steroidogenic pathways, refinements in neonatal screening, improved diagnostic measurements utilizing chromatography and mass spectrometry coupled with steroid profiling, and improved genotyping methods. Clinical trials of alternative medications and modes of delivery have been recently completed or are under way. Genetic and cell-based treatments are being explored. A large body of data concerning long-term outcomes in patients affected by CAH, including psychosexual well-being, has been enhanced by the establishment of disease registries. This review provides the reader with current insights in CAH with special attention to these new developments.

Keywords: CYP21A2; 21-hydroxylase deficiency; Steroid biosynthesis; aldosterone; cortisol; glucocorticoid; mineralocorticoid.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Adrenal Hyperplasia, Congenital* / drug therapy
Adrenal Hyperplasia, Congenital* / therapy
Humans
Hydrocortisone
Infant, Newborn
Mutation
Neonatal Screening
Steroid 21-Hydroxylase / genetics

Substances

CYP21A2 protein, human
Steroid 21-Hydroxylase
Hydrocortisone

Abstract

Publication types

MeSH terms

Substances

Grants and funding